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Fur-Hsing Wen, Chen Hsiu Chen, Wen-Chi Chou, Jen-Shi Chen, Wen-Cheng Chang, Chia-Hsun Hsieh and Siew Tzuh Tang

Background: Issuing do-not-resuscitate (DNR) orders has seldom been an outcome in randomized clinical trials of advance care planning (ACP) interventions. The aim of this study was to examine whether an ACP intervention facilitating accurate prognostic awareness (PA) for patients with advanced cancer was associated with earlier use of DNR orders. Patients and Methods: Participants (n=460) were randomly assigned 1:1 to the experimental and control arms, with 392 deceased participants constituting the final sample of this secondary analysis study. Participants in the intervention and control arms had each received an intervention tailored to their readiness for ACP/prognostic information and symptom-management education, respectively. Effectiveness in promoting a DNR order by facilitating accurate PA was determined by intention-to-treat analysis using multivariate logistic regression with hierarchical linear modeling. Results: At enrollment in the ACP intervention and before death, 9 (4.6%) and 8 (4.1%) participants and 168 (85.7%) and 164 (83.7%) participants in the experimental and control arms, respectively, had issued a DNR order, without significant between-arm differences. However, participants in the experimental arm with accurate PA were significantly more likely than participants in the control arm without accurate PA to have issued a DNR order before death (adjusted odds ratio, 2.264; 95% CI, 1.036–4.951; P=.041). Specifically, participants in the experimental arm who first reported accurate PA 31 to 90 days before death were significantly more likely than their counterparts in the control arm who reported accurate PA to have issued a DNR order in the next wave of assessment (adjusted odds ratio, 13.365; 95% CI, 1.989–89.786; P=.008). Both arms issued DNR orders close to death (median, 5–6 days before death). Conclusions: Our ACP intervention did not promote the overall presence of a DNR order. However, our intervention facilitated the issuance of NDR orders before death among patients with accurate PA, especially those who reported accurate PA 31 to 90 days before death, but it did not facilitate the issuance of DNR orders earlier than their counterparts in the control arm.

ClinicalTrial.gov Identification: NCT01912846

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Amy A. Kirkham, Karen A. Gelmon, Cheri L. Van Patten, Kelcey A. Bland, Holly Wollmann, Donald C. McKenzie, Taryne Landry and Kristin L. Campbell

Background: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. Patients and Methods: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. Results: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54–1.11) or delay (RR, 1.05; 95% CI, 0.62–1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia (P=.027), other infections (P=.049), and fatigue (P=.037) were less common, whereas mucositis was more common (P=.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54–84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P=.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P=.974). Conclusions: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.

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Elliott K. Yee, Natalie G. Coburn, Laura E. Davis, Alyson L. Mahar, Victoria Zuk, Vaibhav Gupta, Ying Liu, Craig C. Earle and Julie Hallet

Background: Little is known about how the geographic distribution of cancer services may influence disparities in outcomes for noncurable pancreatic adenocarcinoma. We therefore examined the geographic distribution of outcomes for this disease in relation to distance to cancer centers. Methods: We conducted a retrospective population-based analysis of adults in Ontario, Canada, diagnosed with noncurable pancreatic adenocarcinoma from 2004 through 2017 using linked administrative healthcare datasets. The exposure was distance from place of residence to the nearest cancer center providing medical oncology assessment and systemic therapy. Outcomes were medical oncology consultation, receipt of cancer-directed therapy, and overall survival. We examined the relationship between distance and outcomes using adjusted multivariable regression models. Results: Of 15,970 patients surviving a median of 3.3 months, 65.6% consulted medical oncology and 38.5% received systemic therapy. Regions with comparable outcomes were clustered throughout Ontario. Mapping revealed regional discordances between outcomes. Increasing distance (reference, ≤10 km) was independently associated with lower likelihood of medical oncology consultation (relative risks [95% CI] for 11–50, 51–100, and ≥101 km were 0.90 [0.83–0.98], 0.78 [0.62–0.99], and 0.77 [0.55–1.08], respectively) and worse survival (hazard ratios [95% CI] for 11–50, 51–100, and ≥101 km were 1.08 [1.04–1.12], 1.17 [1.10–1.25], and 1.10 [1.02–1.18], respectively), but not with likelihood of receiving therapy. Receipt of therapy seems less sensitive to distance, suggesting that distance limits entry into the cancer care system via oncology consultation. Regional outcome discordances suggest inefficiencies within and protective factors outside of the cancer care system. Conclusions: These findings provide a basis for clinicians to optimize their practices for patients with noncurable pancreatic adenocarcinoma, for future studies investigating geographic barriers to care, and for regional interventions to improve access.

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Shaji K. Kumar, Natalie S. Callander, Kehinde Adekola, Larry Anderson, Muhamed Baljevic, Erica Campagnaro, Jorge J. Castillo, Jason C. Chandler, Caitlin Costello, Yvonne Efebera, Matthew Faiman, Alfred Garfall, Kelly Godby, Jens Hillengass, Leona Holmberg, Myo Htut, Carol Ann Huff, Yubin Kang, Malin Hultcrantz, Sarah Larson, Michaela Liedtke, Thomas Martin, James Omel, Kenneth Shain, Douglas Sborov, Keith Stockerl-Goldstein, Donna Weber, Jennifer Keller and Rashmi Kumar

Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. This manuscript discusses the management of patients with solitary plasmacytoma, smoldering multiple myeloma, and newly diagnosed multiple myeloma.

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NCCN Guidelines Insights: Soft Tissue Sarcoma, Version 1.2021

Featured Updates to the NCCN Guidelines

Margaret von Mehren, John M. Kane III, Marilyn M. Bui, Edwin Choy, Mary Connelly, Sarah Dry, Kristen N. Ganjoo, Suzanne George, Ricardo J. Gonzalez, Martin J. Heslin, Jade Homsi, Vicki Keedy, Ciara M. Kelly, Edward Kim, David Liebner, Martin McCarter, Sean V. McGarry, Christian Meyer, Alberto S. Pappo, Amanda M. Parkes, I. Benjamin Paz, Ivy A. Petersen, Matthew Poppe, Richard F. Riedel, Brian Rubin, Scott Schuetze, Jacob Shabason, Jason K. Sicklick, Matthew B. Spraker, Melissa Zimel, Mary Anne Bergman and Giby V. George

The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with soft tissue sarcomas. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including the development of a separate and distinct guideline for gastrointestinal stromal tumors (GISTs); reconception of the management of desmoid tumors; inclusion of further recommendations for the diagnosis and management of extremity/body wall, head/neck sarcomas, and retroperitoneal sarcomas; modification and addition of systemic therapy regimens for sarcoma subtypes; and revision of the principles of radiation therapy for soft tissue sarcomas.

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Emily C. Harrold, Ahmad F. Idris, Niamh M. Keegan, Lynda Corrigan, Min Yuen Teo, Martin O’Donnell, Sean Tee Lim, Eimear Duff, Dearbhaile M. O’Donnell, M. John Kennedy, Sue Sukor, Cliona Grant, David G. Gallagher, Sonya Collier, Tara Kingston, Ann Marie O’Dwyer and Sinead Cuffe

Background: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.9% to 54.3%. Insomnia prevalence has not been previously quantified in an Irish oncology cohort. Methods: A 40-item questionnaire was prospectively administered to ambulatory patients with cancer aged ≥18 years. Prespecified criteria to define insomnia syndrome combined those of the International Classification of Sleep Disorders, version 1, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The Hospital Anxiety and Depression Scale-Depression/Anxiety (HADS-D/A) was used to screen for potential confounding variables. Results: The response rate to the questionnaire was 87% (294/337). The predominant respondent age group was 55 to 64 years (26%; 77/294), 70.7% were female (208/294), and the most common cancer subtypes were breast (37.4%), colorectal (12.9%), and lung (12.2%). A total of 62% (183/294) of patients reported sleep disturbance after diagnosis, 63% (115/183) reported moderate/severe distress related to this disturbance, and 37% (61/183) reported a significant impact on physical function. Although 33% (98/294) met insomnia syndrome criteria, only 34% (33/98) of these patients had a preexisting history of sleep disturbance. Female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A ≥11 were associated with statistically significant higher odds ratios (OR) of insomnia syndrome. Multivariate analysis identified breast cancer (OR, 3.17; P=.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) as independent predictors of insomnia syndrome. Conclusions: Insomnia syndrome prevalence in this cohort is comparable to that reported previously and supports dedicated sleep assessment. This study identifies potentially modifiable risk factors for insomnia and demonstrates additional utility of the HADS score in identifying patients at risk.

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Karam Khaddour, Michael R. Chicoine, Jiayi Huang, Sonika Dahiya and George Ansstas

Craniopharyngiomas are rare tumors that arise in the suprasellar region of the brain and are known for their aggressive nature despite their WHO grade I. This is due to the complex neuroanatomy of the sellar/suprasellar region and their proximity to the optic nerve apparatus, hypothalamic–pituitary tract, and other critical neuroanatomical structures. Definitive treatment is based on a multidisciplinary approach and often involves a combination of surgical, radiation, and medical therapy. However, there is high morbidity associated with surgery and RT due to the complex neuroanatomy of this region. Recently, BRAFV600E somatic mutation has been identified in most papillary craniopharyngiomas. This discovery has led to the novel use of RAF pathway inhibitors to treat these tumors. We report the successful use of dabrafenib (BRAF inhibitor) and trametinib (mitogen-activated protein kinase kinase inhibitor) in the neoadjuvant setting followed by definitive stereotactic radiosurgery. We propose an algorithm based on available literature on the integration of targeted therapy in the management of papillary craniopharyngiomas. Our observations, together with prior case reports, advocate the incorporation of targeted therapy for unresectable craniopharyngiomas and reinforce that treatment with dual-targeted therapy is safe and effective.